Fibrinogen, also known as coagulation factor I, exists in the blood and is an important protein in the process of blood clotting. Fibrinogen has a molecular weight of 340,000 Daltons, and is composed of two subunits connected by disulfide bonds to form a dimer. Each subunit respectively consists of three intertwined polypeptide chains, called the A chain, the B chain, and the C chain. In the process of clotting, fibrinogen is digested by thrombin to generate fibrin and thus form an insoluble fibrin polymer. Then the blood fiber formed from the fibrin polymer and blood platelets will form a solid tampon. Fibrinogen is also a stress protein, whose content in the blood is about 1.5-4 mg/ml. The content of fibrinogen is related to the immune status, which could also reflect the risk of cardiovascular disease.
Fibrinogen-420 is a subtype of fibrinogen, in which the C-terminal of the A chain has an extension of globular domain as compared to the A chain of normal fibrinogen. This globular domain is called the alpha EC domain protein (SEQ ID NO:1) and has high homology with the globular domain at the terminus of the B and C chains. The molecular weight of fibrinogen-420 is about 420,000 Daltons, which is different from the normal tissue fibrinogens (340,000 Daltons).
Protein misfolding disease is a class of diseases which are due to the conformational change of specific protein(s) in the tissue, by which protein(s) aggregate(s) to produce amyloidosis, finally resulting in a class of diseases with pathological changes in tissues and organs, with examples including Alzheimer's disease and bovine spongiform encephalopathy. There have been no effective methods to prevent or treat these diseases by now. The existing methods, such as monoclonal antibody technology, small molecules, synthetic peptides, et al. have many disadvantages including immune rejection reactions, lacking of broad-spectrum, significant side effects, and a short half-life in vivo.
There are a large number of heat shock proteins or chaperones, protect cells from high temperature, free radicals, organic solvents (eg ethanol) and other damages when the body suffers from stimulation. But the heat shock proteins do not exist in the circulatory system. The mechanism by which the body protects extracellular protein is unclear.